Expert Discusses Tissue Versus Liquid Biopsy in Next-Generation Sequencing in Lung Cancer

Lynette M. Sholl, MD

There are benefits and challenges with using either liquid or tissue biopsy for next-generation sequencing in the field of lung cancer, explained Lynette M. Sholl, MD, adding that, regardless of which path is taken, obtaining this genomic data is essential to guiding patient care.

“Now that we have access to a lot of genomic information for our patients, we are realizing that there are a lot of nuances here. It is not just biomarkers that are going to determine outcomes,” said Sholl. “There are a lot of co-mutations that we see together with that principle driver mutation that are potentially affecting outcomes. Being able to have access to that type of genomic data is interesting in the research space and increasingly is beginning to inform the way we think about potentially counseling patients.”

In an interview with OncLive, Sholl, chief of thoracic pathology at Brigham and Women's Hospital, Dana-Farber Cancer Institute, and associate professor at Harvard Medical School, discussed the evolving use of liquid and tissue biopsies for next-generation sequencing in the treatment paradigm for patients with lung cancer.

OncLive: What are some of the differences between the next-generation sequencing technologies being used in this space to detect actionable markers?

Sholl: The difference between these assays essentially boils down to cost and turnaround time. If you have a very discreet number of biomarkers that you are interested in you could look for those in a matter of a few days once you have the tissue, plasma, or blood sample on hand. You can look for those targeted biomarkers very quickly and at low costs.

The downside is that you only get what you look for, so you are going to miss more of the nuanced information that is available with a larger next-generation sequencing panel. Although, the downside to these larger panels is that they tend to take longer, often about a week or 2 just for the technical component of that testing to be completed. Of course, they are much more complicated to interpret because there is a large volume of data that is generated from these large panels.

What is the role of liquid biopsy in lung cancer? How do you see these tests being utilized in this space in the future?

One of the biggest challenges we face in the lung cancer space is the availability of tissue for complete biomarker characterization. Patients will often undergo minimally invasive procedures to get diagnostic tissue and those are typically very small biopsies. The great thing about minimally invasive procedures is that they are minimally invasive, and they have a relatively small number of adverse events for the patients in terms of bleeding or other complications. The downside, of course, is that you do not get much material to work with. You have a little bit of material to make your diagnosis and then you are trying to squeeze a lot more information out of those tissues. We end up seeing somewhere around 30% of tissue biopsies actually being insufficient to generate complete biomarker testing in our lung cancer patients. That is where the strength of liquid biopsy emerges.

There is a great debate in the field of when and where to perform liquid biopsy testing. It is very useful, for instance, in the relapse setting. The gold standard clinical approach is that you have a patient with an EGFR mutation who goes onto relapse. When we were using first-generation EGFR TKIs, there was one specific mutation that we were looking for to make the next determination in terms of treatment—the T790M mutation. You could easily do a liquid biopsy to look for that specific mutation. It is a bit more of a complex space now because you need a more comprehensive panel in the liquid biopsy space in order to make that same paradigm work.

But we are increasingly seeing liquid biopsy move into the field in a much broader sense. We see it being used after a diagnosis is made to generate that first look at the biomarkers. It can be complementary to a tissue biopsy and sometimes you will get more information from the liquid biopsy than the tissue biopsy because you do not have enough tissue left over to do molecular testing.

In other cases, we find that because the patient's tumor does not necessarily shed into the bloodstream much you do not actually see those tumor mutations in the blood, and you have to rely on tissue biopsy in order to make a treatment determination. Oftentimes, because liquid biopsies are very easy to obtain in the clinic and they do not require a lot of material management as you need for tissue biopsies, clinicians will obtain a liquid biopsy. If it is informative, they can proceed with treatment accordingly and if it is not, they may proceed to tissue relapse or try to obtain archival tissue for biomarker testing.

Is there any research you are currently working on that you would like to highlight?

Regarding how patients might respond I would say one particular example is the identification of p53 mutations at the same time that you identify an EGFR mutation. We are now recognizing that those patients do not do as well with EGFR TKIs. They tend to relapse a little bit sooner so knowing that information up front helps to plan or counsel the patient on the likelihood of their response to therapy. There are dozens of other examples like that that we will see emerging in the literature.